BGE CORE SUMMARY: The goal of the Biomarkers, Genomics and Epigenomics (BGE) Core is to facilitate and co-ordinate biospecimen analysis across Projects 1-3 within the WNY Center for Research on Flavored Tobacco Products (CRoFT) to strengthen the overall themes and enhance scientific productivity. The main focus of the BGE core is to provide centralized workflow standards for in vitro and in vivo exposure from electronic nicotine delivery systems (ENDS)/cigarillos/waterpipe tobacco and to determine biomarkers of exposure and potential harm in biofluids, primary cells and tissues. These synchronized efforts will increase efficacy and ensure valid, high precision protocols and reproducible methods around flavored tobacco products suitable for the regulatory needs of the FDA-CTP. We have provided evidence that shows altered systemic biomarkers, genomic and epigenomic signatures in air vs. tobacco/cigarette smoke (CS) exposed mouse and human non-smokers vs. smokers confirmed by luminex, ELISA, mass spectrometry, genomics and epigenomics approaches. We are aware that flavored tobacco products can affect systemic biomarkers of potential harm including genomic and epigenomic signatures that will be investigated under specific aims 1-3: Aim 1: Standardize experimental conditions, focusing on laboratory testing, biochemical assays and analytical methods to measure biomarkers of potential harm from exposure to flavored tobacco products. We will obtain biospecimens/samples from Projects (1-3) to analyze for biomarkers of exposure and potential harm (toxicity) including standard biochemical assays. In addition, BGE core will support the human studies to verify the nicotine intake, exposure status of tobacco products in plasma, saliva and urine samples. Aim 2: Develop standard bioassays to identify existing/known and newer circulating biomarkers in biological fluids, primary cells and pre-clinical mouse models using genomic and epigenomic approaches. We will assess existing biomarkers as well as develop methods for identification of novel biomarkers (extracellular vesicle/exosomes) of exposure/potential harm using cutting-edge genomics and epigenomics approaches to guide regulation of flavored tobacco products. Aim 3: Develop a multivariate toxicity ranking system based on the assessment of toxicity/biological effects/health outcomes measured from flavored tobacco products. We will develop a multivariate toxicity ranking systems based on biomarkers of potential harm, genomic and epigenomic signatures assessed by the BGE core along with the involvement of BI (Biostatistics and Informatics) core for in-depth biostatistical analysis. The overall goal of BGE core is to provide novel technologies needed for testing biomarkers in the biofluids, primary cells and pre-clinical models. BGE core will provide a central resource for development and performance of assays as per good laboratory practice (GLP) standards relevant for informing the FDA?s regulation of the manufacture, distribution and marketing of flavored tobacco products to protect public health.